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AIMS AND OBJECTIVES: To evaluate perceived stress, concern about hypoglycaemia and the level of knowledge of management of the disease in patients with type 1 diabetes mellitus and their relationship with glycaemic control, gender and age. BACKGROUND: Perceived stress and concern about hypoglycaemia are significant obstacles to achieving adequate glycaemic control in patients with type 1 diabetes mellitus, and notably influence management of the disease itself. MATERIAL AND METHODS: A cross-sectional study was carried out in 193 adult patients with type 1 diabetes mellitus. Study quality was scored using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. Glycaemic control was evaluated by number and type of hypoglycaemic event and glycosylated haemoglobin. Questionnaires about hypoglycaemia concern (HFS II), perceived stress (PSS), unrecognised hypoglycaemia (Clarke Test) and level of knowledge of the disease were completed. RESULTS: Perceived stress was significantly associated with glycosylated haemoglobin (p < 0.001) and concern about hypoglycaemia (p < 0.037). With respect to level of knowledge, we observed that an advanced level was associated with lower glycosylated haemoglobin (p < 0.001), number (p < 0.001) and type (p < 0.001) of hypoglycaemic episode, and less perceived stress (p = 0.006). In addition, age was negatively correlated with perceived stress (p < 0.030) and positively correlated with the number of unrecognised hypoglycaemic episodes (p < 0.002), which was associated, in turn, with a higher number of daily glycaemia tests (p < 0.037) and concern about hypoglycaemia (p < 0.006). CONCLUSION: In type 1 diabetes mellitus, perceived stress can negatively influence glycaemic control and concern about hypoglycaemia, and level of knowledge about the condition has a bearing on glycosylated haemoglobin levels, perceived stress and number and type of hypoglycaemic events. In addition, higher age is associated with more frequent unrecognised hypoglycaemic events. RELEVANCE TO CLINICAL PRACTICE: It is essential to identify and address the psychological needs of patients with type 1 diabetes mellitus with the aim of achieving an adequate management of the disease itself and generating a change in future intervention strategies.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Adulto , Humanos , Hemoglobina Glucada , Control Glucémico , Estudios Transversales , Hipoglucemiantes , Estrés Psicológico , InsulinaRESUMEN
Head and neck cancer (HNC) is among the ten most frequent tumours, with 5-year survival rates varying from 30% to 70% depending on the stage and location of the tumour. HNC is traditionally known as head and neck squamous cell carcinoma (HNSCC), since 90% arises from epithelial cells. Metastasis remains a major cause of mortality in patients with HNSCC. HNSCC patients with metastatic disease have an extremely poor prognosis with a survival rate of less than a year. Matrix metalloproteinases (MMPs) have been described as biomarkers that promote cell migration and invasion. Radiotherapy is widely used to treat HNSCC, being a determining factor in the alteration of the tumour's biology and microenvironment. This review focuses on analysing the current state of the scientific literature on this topic. Although few studies have focused on the role of these proteinases in HNC, some authors have concluded that radiotherapy alters the behaviour of MMPs and tissue inhibitors of metalloproteinases (TIMPs). Therefore, more research is needed to understand the roles played by MMPs and their inhibitors (TIMPs) as prognostic biomarkers in patients with HNC and their involvement in the response to radiotherapy.
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Neoplasias de Cabeza y Cuello , Oncología por Radiación , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Pronóstico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Metaloproteinasas de la Matriz , Microambiente TumoralRESUMEN
We aimed to assess the relationships among the adipose tissue's (AT) oxidative microenvironment, in situ accumulated persistent organic pollutant (POP) concentrations, and cancer development. POP and oxidative stress levels were quantified in AT samples from 382 adults recruited within the GraMo cohort (2003-2004) in Granada (Spain). The 16-year cancer incidence was ascertained by reviewing health/administrative databases. Cox-regression models and mediation analyses were performed. The enzymes superoxide dismutase (SOD) and glutathione reductase (GRd) were positively associated with the risk of non-hormone-dependent (NHD) cancer [adjusted hazard ratio (HR) 1.76; 95% confidence interval (CI): 1.17, 2.64 and HR 2.35; 95% CI: 1.41, 3.94, respectively]. After adjustment for covariates, polychlorinated biphenyl-138 (PCB-138) (HR 1.78; 95% CI: 1.03, 3.09), ß-hexachlorocyclohexane (ß-HCH) (HR 1.70; 95% CI: 1.09, 2.64), and hexachlorobenzene (HR 1.54; 95% CI: 1.02, 2.33) were also positively associated with the risk of NHD cancer. Although confidence intervals included the null value, probably because of the modest number of cancer cases, we observed a potential mediation effect of SOD and GRd on the associations between ß-HCH and the risk of NHD tumors (percent mediated = 33 and 47%, respectively). Our results highlight the relevance of human AT's oxidative microenvironment as a predictor of future cancer risk as well as its potential mediating role on POP-related carcinogenesis. Given their novelty, these findings should be interpreted with caution and confirmed in future studies.
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Contaminantes Ambientales , Hidrocarburos Clorados , Neoplasias , Plaguicidas , Bifenilos Policlorados , Tejido Adiposo/metabolismo , Adulto , Contaminantes Ambientales/metabolismo , Humanos , Hidrocarburos Clorados/metabolismo , Incidencia , Neoplasias/inducido químicamente , Neoplasias/epidemiología , Oxidación-Reducción , Contaminantes Orgánicos Persistentes , Plaguicidas/metabolismo , Bifenilos Policlorados/metabolismo , Microambiente TumoralRESUMEN
Docker containers are the lightweight-virtualization technology prevailing today for the provision of microservices. This work raises and discusses two main challenges in Docker containers' scheduling in cloud-fog-internet of things (IoT) networks. First, the convenience to integrate intelligent containers' schedulers based on soft-computing in the dominant open-source containers' management platforms: Docker Swarm, Google Kubernetes and Apache Mesos. Secondly, the need for specific intelligent containers' schedulers for the different interfaces in cloud-fog-IoT networks: cloud-to-fog, fog-to-IoT and cloud-to-fog. The goal of this work is to support the optimal allocation of microservices provided by the main cloud service providers today and used by millions of users worldwide in applications such as smart health, content delivery networks, smart health, etc. Particularly, the improvement is studied in terms of quality of service (QoS) parameters such as latency, load balance, energy consumption and runtime, based on the analysis of previous works and implementations. Moreover, the scientific-technical impact of smart containers' scheduling in the market is also discussed, showing the possible repercussion of the raised opportunities in the research line.
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AIM: To evaluate the efficacy of radiation therapy in alleviating pain and improving the quality of life (QoL) with validated questionnaires in patients with painful bone metastases (BoM). METHODS: This prospective, observational study recruited 167 patients with painful BoM who were treated with palliative radiotherapy (PRT) from February 2015 to February 2018. After the first clinical assessment, the patients filled out specific questionnaires and underwent a fast radiotherapy treatment within 48 hours. The patients were followed up for eight weeks. RESULTS: The median age was 66.30 years. The most common primary cancer was lung cancer (31.1%). The most often prescribed scheme was 8 Gy in one fraction (70%). The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation. Overall, reduced pain and drug score were reported at two weeks of PRT in 68 (51.5%) and 37 (28%) of patients, respectively. CONCLUSIONS: PRT is an effective treatment option for patients with painful BoM.
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Neoplasias Óseas/radioterapia , Dolor en Cáncer/radioterapia , Calidad de Vida/psicología , Radioterapia Conformacional , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/psicología , Neoplasias Óseas/secundario , Dolor en Cáncer/psicología , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Cuidados Paliativos/métodos , Estudios Prospectivos , Dosificación Radioterapéutica , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. METHODS: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. RESULTS: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. CONCLUSION: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/diagnóstico , Exosomas/genética , MicroARNs/sangre , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/aislamiento & purificación , Mama/diagnóstico por imagen , Mama/cirugía , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Exosomas/patología , Estudios de Factibilidad , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Biopsia Líquida/métodos , MicroARNs/genética , MicroARNs/aislamiento & purificación , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Células Neoplásicas Circulantes/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: We have recently shown that radiotherapy may not only be a successful local and regional treatment but, when combined with MSCs, may also be a novel systemic cancer therapy. This study aimed to investigate the role of exosomes derived from irradiated MSCs in the delay of tumor growth and metastasis after treatment with MSC + radiotherapy (RT). METHODS: We have measured tumor growth and metastasis formation, of subcutaneous human melanoma A375 xenografts on NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2 Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without any treatment. Using proteomic analysis, we studied the cargo of the exosomes released by the MSC treated with 2 Gy, compared with the cargo of exosomes released by MSC without treatment. RESULTS: The tumor cell loss rates found after treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% % and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased the mice surviving time 22,5% in this group, with regard to the group of mice treated with exclusive RT and in a 45,3% respect control group. Moreover, the number of metastatic foci found in the internal organs of the mice treated with MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that the exosome secreted by the MSC, could be implicated in tumor growth delay and metastasis control after treatment. CONCLUSIONS: Our results show that exosomes derived form MSCs, combined with radiotherapy, are determinant in the enhancement of radiation effects observed in the control of metastatic spread of melanoma cells and suggest that exosome-derived factors could be involved in the bystander, and abscopal effects found after treatment of the tumors with RT plus MSC. Radiotherapy itself may not be systemic, although it might contribute to a systemic effect when used in combination with mesenchymal stem cells owing the ability of irradiated MSCs-derived exosomes to increase the control of tumor growth and metastasis.
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Exosomas/metabolismo , Melanoma/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/citología , Radioterapia/métodos , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Terapia Combinada , Humanos , Células MCF-7 , Melanoma/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos NOD , Ratones SCID , Metástasis de la Neoplasia , Proteómica , Resultado del Tratamiento , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors with the potential to improve the healing of chronic wounds. This is the first update of a review first published in 2012. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: In June 2015, for this first update, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library): Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We also searched for ongoing and unpublished clinical trials in the WHO International Clinical Trials Registry Platform (ICTRP) (searched January 2015). We did not impose any restrictions with respect to language, date of publication, or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. We did not apply any date or language restrictions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology, including two reviewers independently selecting studies for inclusion, extracting data, and assessing risk of bias. MAIN RESULTS: The search identified one new RCT, making a total of 10 included RCTs (442 participants, 42% women). The median number of participants per RCT was 29 (range 10 to 117). Four RCTs recruited people with a range of chronic wounds; three RCTs recruited people with venous leg ulcers, and three RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range 8 to 40 weeks).It is unclear whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment (with or without placebo) (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.95 to 1.50; I(2) = 27%, low quality evidence, 8 RCTs, 391 participants). Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care (with or without placebo) (RR 1.22, 95% CI 1.01 to 1.49; I(2) = 0%, low quality evidence, 2 RCTs, 189 participants). It is unclear if autologous PRP affects the healing of venous leg ulcers (RR 1.02, 95% CI 0.81 to 1.27; I(2) = 0% ). It is unclear if there is a difference in the risk of adverse events in people treated with PRP or standard care (RR 1.05, 95% CI 0.29 to 3.88; I(2) = 0%, low quality evidence from 3 trials, 102 participants). AUTHORS' CONCLUSIONS: PRP may improve the healing of foot ulcers associated with diabetes, but this conclusion is based on low quality evidence from two small RCTs. It is unclear whether PRP influences the healing of other chronic wounds. The overall quality of evidence of autologous PRP for treating chronic wounds is low. There are very few RCTs evaluating PRP, they are underpowered to detect treatment effects, if they exist, and are generally at high or unclear risk of bias. Well designed and adequately powered clinical trials are needed.
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Pie Diabético/terapia , Transfusión de Plaquetas/métodos , Plasma Rico en Plaquetas , Úlcera Varicosa/terapia , Cicatrización de Heridas , Adulto , Transfusión de Sangre Autóloga/métodos , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
We report two cases of an axial osteosclerosis with histopathologic findings of osteomesopyknosis in siblings. Osteomesopyknosis is a benign hereditary osteosclerosis that can show a radiologic pattern similar to blastic metastatic disease. The aim of this article is to inform radiologists about the existence of this benign condition and its various radiologic manifestations. Therefore, we discuss the principal differential diagnosis and point out the key imaging findings of osteomesopyknosis in order to avoid overdiagnosis in future cases.
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Hiperostosis/diagnóstico , Osteosclerosis/diagnóstico , Neoplasias de la Columna Vertebral/diagnóstico , Neoplasias de la Columna Vertebral/secundario , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Tomografía Computarizada por Rayos X/métodosRESUMEN
The aim of this study was to assess the influence of adipose tissue concentrations of a group of persistent organic pollutants (POPs) on the risk of hypertension in an adult cohort of residents of Granada (Southern Spain) over a 10-year follow-up. No chemical was significantly associated with the risk of hypertension in the overall population or when models were stratified by sex or median age. However, we found positive associations between log-transformed POP concentrations and hypertension risk in participants with body mass index (BMI) above the median value of 26.3kg/m(2), which were statistically significant for hexachlorobenzene (HR=1.26, 95% CI=1.03-1.56), ß-hexachlorocyclohexane (HR=1.25, 95% CI=1.03-1.51), and polychlorinated biphenyl congeners -138 (HR=1.32, 95% CI=1.04-1.69) and -153 (HR=1.36, 95% CI=1.00-1.84). Inverse associations were observed in the subgroup with BMI≤26.3kg/m(2), but none was statistically significant. More research and a longer follow-up period are warranted to verify these associations and elucidate the role of obesity as a potential effect modifier. Given the elevated worldwide frequency of POP exposure and hypertension, the public health impact of this relationship may be substantial.
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Presión Sanguínea/efectos de los fármacos , Exposición a Riesgos Ambientales , Contaminantes Ambientales/toxicidad , Hidrocarburos Clorados/toxicidad , Hipertensión/epidemiología , Insecticidas/toxicidad , Bifenilos Policlorados/toxicidad , Tejido Adiposo/química , Adulto , Anciano , Índice de Masa Corporal , Monitoreo del Ambiente , Femenino , Humanos , Hipertensión/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Lung cancer remains one of the most prevalent forms of cancer. Radiotherapy, with or without other therapeutic modalities, is an effective treatment. Our objective was to report on the use of radiotherapy for lung cancer, its variability in our region, and to compare our results with the previous study done in 2004 (VARA-I) in our region and with other published data. METHODS: We reviewed the clinical records and radiotherapy treatment sheets of all patients undergoing radiotherapy for lung cancer during 2007 in the 12 public hospitals in Andalusia, an autonomous region of Spain. Data were gathered on hospital, patient type and histological type, radiotherapy treatment characteristics, and tumor stage. RESULTS: 610 patients underwent initial radiotherapy. 37% of cases had stage III squamous cell lung cancer and were treated with radical therapy. 81% of patients with non-small and small cell lung cancer were treated with concomitant chemo-radiotherapy and the administered total dose was ≥60 Gy and ≥45 Gy respectively. The most common regimen for patients treated with palliative intent (44.6%) was 30 Gy. The total irradiation rate was 19.6% with significant differences among provinces (range, 8.5-25.6%; p<0.001). These differences were significantly correlated with the geographical distribution of radiation oncologists (r=0.78; p=0.02). Our results were similar to other published data and previous study VARA-I. CONCLUSIONS: Our results shows no differences according to the other published data and data gathered in the study VARA-I. There is still wide variability in the application of radiotherapy for lung cancer in our setting that significantly correlates with the geographical distribution of radiation oncologists.
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Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estadificación de Neoplasias , Dosificación Radioterapéutica , Estudios Retrospectivos , España , Resultado del TratamientoRESUMEN
Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.
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Células Endoteliales , Melanoma , Neoplasias de la Úvea , beta Catenina , beta Catenina/genética , beta Catenina/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Células Endoteliales/metabolismo , Melanoma/patología , Proteómica , Neoplasias de la Úvea/patología , Factor de Transcripción 4/metabolismoRESUMEN
Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.
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BACKGROUND: Autologous platelet-rich plasma (PRP) is a treatment that contains fibrin and high concentrations of growth factors and has the potential to aid wound healing. OBJECTIVES: To determine whether autologous PRP promotes the healing of chronic wounds. SEARCH METHODS: We searched the Cochrane Wounds Group Specialised Register (searched 15 August 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8); Ovid MEDLINE (1950 to August Week 1 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, August 14, 2012); Ovid EMBASE (1980 to 2012 Week 32); EBSCO CINAHL (1982 to 10 August 2012) and International Clinical Trials Registry Platform (ICTRP)(accessed 22 August 2012). No date or language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared autologous PRP with placebo or alternative treatments for any type of chronic wound in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed each study against the inclusion criteria, extracted data and assessed risk of bias for all included trials. We calculated the risk ratio (RR) or the mean difference (MD) and time to wound healing was analysed as survival data using the hazard ratio (HR). We considered heterogeneity as significant when I(2) was >75%. MAIN RESULTS: Nine eligible RCTs were included, with a total of 325 participants of whom 44% were women. The median number of participants per RCT was 26 (range 10 to 86). Four RCTs recruited people with mixed chronic wounds (there were participants with wounds caused by more than one aetiology and participants who had wounds of several aetiologies in the same trial), three RCTs recruited people with venous leg ulcers and two RCTs considered foot ulcers in people with diabetes. The median length of treatment was 12 weeks (range eight to 40 weeks).One study was at low risk of bias, three studies were at high risk of bias with the remainder being at overall unclear risk of bias. The proportion of completely healed chronic wounds was reported in seven RCTs that compared PRP with standard treatment or placebo, with no statistically significant difference between the groups, in diabetic foot ulcers (RR 1.16; 95% CI 0.57 to 2.35), in venous leg ulcers (pooled RR 1.02; 95% CI 0.81 to 1.27; I(2)=0% ) and in mixed chronic wounds (pooled RR 1.85; 95% CI 0.76 to 4.51; I(2)=42%). The total area epithelialised at the end of the intervention was reported in three RCTs of mixed chronic wounds, there was no statistically significant difference between the groups (pooled MD -1.94 cm(2); 95% CI -4.74 to 0.86; I(2)=47%). The percentage of wound area healed was reported in two RCTs of mixed chronic wounds, and results were statistically significant in favour of the PRP group (RR 51.78%; 95% CI 32.70 to 70.86; I(2)= 0%). Wound complications like infection or necrosis were reported by three RCTs, and there was no statistically significant difference between groups (RR 1.08; 95% CI 0.31 to 3.73). Adverse effects were reported by three studies and there was no statistically significant difference between people treated with PRP and those not given PRP (pooled RR 1.07; 95% CI 0.32 to 3.58; I(2)=0%). AUTHORS' CONCLUSIONS: There is currently no evidence to suggest that autologous PRP is of value for treating chronic wounds. However, current evidence is based on a small number of RCTs, most of which are either at high or unclear risk of bias. Well-designed and adequately powered clinical trials are needed.
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Pie Diabético/terapia , Transfusión de Plaquetas/métodos , Plasma Rico en Plaquetas , Úlcera Varicosa/terapia , Cicatrización de Heridas , Adulto , Transfusión de Sangre Autóloga/métodos , Enfermedad Crónica , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM: To validate the psychometric properties of a questionnaire to measure adherence to treatment among people with type 1 diabetes mellitus and to evaluate its relationship with metabolic control. DESIGN: A cross-sectional study of 167 adult people with type 1 diabetes mellitus recruited from the Endocrinology Service of University Hospital Doctor Peset (Spain). METHODS: The validity of the content, construct and reliability of the instrument were evaluated and the results correlated with levels of glycosylated haemoglobin. RESULTS: The questionnaire was composed of 25 items and 5 dimensions, with a score of 25-150 points and an internal consistency of 0.92, according to Cronbach's coefficient α. The content of validity ratio and the construct (exploratory functional analysis, Kaiser-Meyer-Olkin index and Barlett's spherical test) were adequate. We observed a significant correlation between glycosylated haemoglobin levels and treatment adherence. CONCLUSION: The questionnaire to measure adherence to treatment in type 1 diabetes mellitus is consistent, reliable and valid, showing an excellent association with degree of metabolic control.
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Diabetes Mellitus Tipo 1 , Adulto , Estudios Transversales , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada , Humanos , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients' respiratory capacity and increase the expectations of their cure.
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Rayos gamma , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/efectos de la radiación , Síndrome de Dificultad Respiratoria/terapia , Anexina A1/metabolismo , Betacoronavirus/aislamiento & purificación , COVID-19 , Ensayos Clínicos como Asunto , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Exosomas/metabolismo , Humanos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Pandemias , Neumonía Viral/terapia , Neumonía Viral/virología , Síndrome de Dificultad Respiratoria/patología , Síndrome de Dificultad Respiratoria/virología , SARS-CoV-2RESUMEN
BACKGROUND: Lumbar radiculopathy is a nerve root disorder whose correct diagnosis is essential. The objective of the present study was to analyze the reliability diagnostic validity of eight neurodynamic and/or orthopedic tension tests using magnetic resonance imaging as the Gold Standard. METHODS: An epidemiological study of randomized consecutive cases which was observational, descriptive, transversal, double blinded and was conducted following the Standards for Reporting Diagnostic accuracy studies (STARD) declaration. The sample size was 864 participants. Internal and external validity (CI = 95%) and reliability, were calculated for all tests performed independently. The diagnostic validity of the combined and multiple tests in parallel was also calculated. RESULTS: The analysis indicated that only two tests performed independently had external validity, but neither had reliability or precision. The Straight Leg Raise test and the Bragard test performed in a multiple parallel way showed high sensitivity (97,40%), high negative predictive value (PV- 96,64%) and external validity (Likelihood Ratio- 0,05). The combined test of the Slump test and the Dejerine's triad had internal and external validity. CONCLUSIONS: The Straight Leg Raise test and the Bragard test performed in a multiple parallel way and the combined test of the Slump Test and the Dejerine's triad have clinical validity to discard lumbar or lumbar-sacral radiculopathy.
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Dolor de la Región Lumbar/diagnóstico , Vértebras Lumbares/diagnóstico por imagen , Región Lumbosacra/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Examen Neurológico/métodos , Examen Físico/métodos , Radiculopatía/diagnóstico por imagen , Raíces Nerviosas Espinales/diagnóstico por imagen , Prueba de Esfuerzo , Femenino , Humanos , Dolor de la Región Lumbar/etiología , Masculino , Radiculopatía/diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Autologous plasma rich in platelets (PRP) is a derived blood product whose application in clinical practice is growing. A systematic review was conducted to evaluate its efficacy and safety. STUDY DESIGN AND METHODS: A search was performed in electronic databases. Randomized controlled clinical trials (RCTs) in adult patients were included and assessed for methodologic quality. The main outcomes were "tissue regeneration" and "safety." Relative risks (RRs) and standardized mean differences (SMDs) were calculated to show pooled estimates for these outcomes. When the results heterogeneity was more than 50 percent, a sensitivity analysis was performed. RESULTS: Twenty RCTs were included (11 of oral and maxillofacial surgery, 7 of chronic skin ulcers, and 2 of surgery wounds). Four RCTs evaluated the depth reduction in gingival recession in chronic periodontitis; the SMD was 0.54 (95% confidence interval [CI], 0.16 to 0.92) mm, favorable to PRP. Three RCTs evaluated the clinical attachment level in chronic periodontitis; the SMD was 0.33 (95% CI, -0.71 to 1.37) mm. Six RCTs assessed the complete skin epithelialization in wound ulcers; the RR was 1.40 (95% CI, 0.85 to 2.31). Only 6 RCTs reported adverse effects without differences between groups. CONCLUSIONS: PRP improves the gingival recession but not the clinical attachment level in chronic periodontitis. In the complete healing process of chronic skin ulcers, the results are inconclusive. There are little data about PRP safety. There are several methodologic limitations and, consequently, future research should focus on strong and well-designed RCTs that assess the efficacy and safety of PRP.
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Transfusión de Sangre Autóloga , Transfusión de Plaquetas , Seguridad , Cicatrización de Heridas , Enfermedad Crónica , Periodontitis Crónica/cirugía , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Úlcera Cutánea/terapia , Cirugía Bucal/métodosRESUMEN
In this paper, we summarize published articles and experiences related to the attempt to improve radiotherapy outcomes and, thus, to personalize the radiation treatment according to the individual characteristics of each patient. The evolution of ideas and the study of successively published data have led us to envisage new biophysical models for the interpretation of tumor and healthy normal tissue response to radiation. In the development of the model, we have shown that when mesenchymal stem cells (MSCs) and radiotherapy are administered simultaneously in experimental radiotherapy on xenotumors implanted in a murine model, the results of the treatment show the existence of a synergic mechanism that is able to enhance the local and systemic actions of the radiation both on the treated tumor and on its possible metastasis. We are convinced that, due to the physical hallmarks that characterize the neoplastic tissues, the physical-chemical tropism of MSCs, and the widespread functions of macromolecules, proteins, and exosomes released from activated MSCs, the combination of radiotherapy plus MSCs used intratumorally has the effect of counteracting the pro-tumorigenic and pro-metastatic signals that contribute to the growth, spread, and resistance of the tumor cells. Therefore, we have concluded that MSCs are appropriate for therapeutic use in a clinical trial for rectal cancer combined with radiotherapy, which we are going to start in the near future.